Project Summary: Persons with non-small cell lung cancer (NSCLC) report significantly more unmet supportive care needs than other cancer populations, yet they are among the most vulnerable and least studied. Two of the most prevalent unmet supportive care needs include overcoming fatigue and attaining adequate exercise to meet physical demands of daily living. Cancer-related fatigue (CRF) is a prevalent, persistent, and distressing symptom in the NSCLC population. CRF correlates with greater severity of 15 other symptoms, leading to lower physical function for persons with NSCLC. Among 13 core symptoms across 3,106 breast, colorectal, prostate, and lung cancer patients, persons with lung cancer were the most symptomatic, with moderate to severe fatigue being reported with the greatest prevalence. While surgery is the standard curative treatment for NSCLC, no formal guidelines exist for post-surgical rehabilitation. We propose a randomized controlled trial (RCT) of a novel rehabilitative intervention for persons with NSCLC after surgery. Our intervention promotes self-management of CRF and tests the intervention's impact on CRF severity and fatigability with analysis by age. Our preliminary data included a two-arm RCT (R21 CA164515) incorporating the proposed intervention, where we exceeded goals for recruitment (67%), retention (97%), adherence (93%), and acceptability. Our 6-wk exercise intervention demonstrated preliminary efficacy in significantly reducing CRF severity and fatigability as compared to usual care, with mean CRF levels restored to levels lower than pre-surgery. The exercise group's functional performance exceeded usual care. No adverse events were reported; participants had a mean age of 67 with a mean of 8 comorbid conditions. Our long-term goal is to develop interventions to increase perceived self-efficacy for CRF self-management in order to improve CRF, symptom status, functional status, and quality of life (QOL) for persons with NSCLC. Our objective in this application is to determine the efficacy, optimal timing, and sustainability of our innovative home-based exercise intervention. This study has the potential to transform the current standard by providing a rehabilitative exercise intervention after surgery. The intervention is home-based, self-paced, and builds in duration upon discharge from the hospital after surgery. Aim 1: Determine efficacy by comparing the immediate intervention group with wait-list control (usual care) and attention control by age. Aim 2: Determine efficacy of initiating the exercise intervention 6 wks post-discharge and compare results with the immediate intervention group for all ages. Aim 3: Determine the immediate intervention's sustainability by analyzing 3a) rates of extension, adherence, and retention; 3b) acceptability; and 3c) efficacy of primary and secondary outcomes. IMPACT: Our results will provide a novel exercise intervention, and its optimal timing, and fills the gap for a vulnerable population by providing a practical, portable, and low-cost means of reducing CRF severity and fatigability that is enjoyable and applicable to nearly all post-thoracotomy lung cancer patients.